1-bromo2,2,2-trifluoroethyl difluoromethyl ether as an inhalation anesthetic

ABSTRACT

The novel compound 1-bromo-2,2,2-trifluoroethyl difluoromethyl ether having the formula CF3CHBr-O-CHF2 is prepared through bromination of 2,2,2-trifluoroethyl difluoromethyl ether. The brominated compound is useful as an inhalation anesthetic and as a solvent and dispersant for fluorinated materials.

United States Patent I 1 1 3,764,705

Terrell Oct. 9, 1973 l-BROMO2,2,2-TRIFLUOROETHYL 3,535,425 10/1970 Terrell 424/342 DIFLUOROMETHYL ETHER AS AN INHALATION ANESTHETIC [75] Inventor: Ross C. Terrell, Plainfield, NJ. [73] Assignee: Airco, Inc., New York, N.Y.

[22] Filed: May 3, 1971 [21] Appl. No.: 139,862

52 U.S. Cl 424/342, 260/614 F [51] Int. Cl A61b 27/00 [58] Field of Search 424/342; 260/614 F [56] References Cited UNITED STATES PATENTS 3,449,504 6/1969 Terrell .1 260/614 F 3,586,724 6/1971 Terrell 424/342 Primary Examiner-Jerome D. Goldberg Attorney-Roger M. Rathbun, Edmund W. Bopp and H. Hume Mathews [57] ABSTRACT The novel compound l-bromo-2,2,2-trifluoroethyl difluoromethyl ether having the formula CF CHBr-O-CHF is prepared through bromination of 2,2,2-trifluoroethyl difluoromethyl ether. The brominated compound is useful as an inhalation anesthetic and as a solvent and dispersant for fluorinated materials.

3 Claims, No Drawings 1 1-BROMO-2,2,2-TRIFLUOROETHYL This ether is normally a clear, colorless liquid with a not unpleasant odor, and has the following physical properties: boiling point 64.5 C.; vapor pressure 175 mm. at 25 C.; specific gravity 1.9; refractive index N 1.3297 and molecular weight 229. The compound 'is nonflammable, soda lime stable, and a potent anesthetic for anesthetic-susceptible mammals. This ether is also easily miscible with other organic liquids including fats and oils and has useful solvent properties, for example, as a solvent for fluorinated olefins and other fluorinated materials such as fluoro waxes. The compound may be used to prepare pastes and dispersions of such materials useful for coatings and the like and may be used as a degreasing agent.

The compound l-bromo-2,2,Z-trifluorothyl difluoromethyl ether can be prepared by brominating 2,2,2-trifluoroethyl difluoromethyl ether, i.e., CH Cl-l- OCHF whose preparation is described in U.S. Pat. No. 3,535,425. The bromination can be carried out at temperatures of about 425 to 500 C., and best results are usually found at about 450 to 475 C. Following the bromination the reaction mass can be separated by fractional distillation or by vapor phase chromatography.

The following example will illustrate the preparation of l-bromo-2,2,2-trifluoroethyl difluoromethyl ether.

The feed ether, CH CH -O-CHF (76 g.), was charged to a bubbler. Nitrogen at 5-10 liters per hour, was passed through the bubbler and into another bubbler containing bromine. The resulting ether and bromine-containing gas stream was then passed through a 1 inch X 12 inch glass tube maintained at 450 C. by an electrical heater. The product was collected in a trap at 7 8 C. After 6 hours, 73 grams of CH Cl-l -O-CHF and 41 g. of bromine had been reacted. The product was recovered by distillation and preparative gas chromatography, bp. 64.5 C., N 1.3297.

Calculated Formulation C H BrF O: C, l5.7: H, 0.87

Found: C,l6.0; H, 0.89 The desired compound was further identified by infrared spectra.

In order to determine the potency of l-bromo-2,2,2- trifluoroethyl difluoromethyl ether as an inhalation anesthetic in combination with oxygen, tests were carried out on mice. The 1-bromo-2,2,2-trifluoroethyl difluoromethyl ether used was at least 99.5 percent pure as determined by vapor phase chromatography.

In the tests, groups of five mice were placed into a jar and exposed to a concentration of 0.5 to 2.5 percent by volume of l-bromo-2,2,2-trifluoroethyl difluoromethyl ether. After an induction time which was free of excitation, the mice were anesthetized and then recovered. The results of these pharmacologic tests were as follows:

No. of

Animals lnhal. lnduc. Recovery Conc.

Tested 5 0.5%

* rn minutes seconds 1 Tail clip test reaction to pain created by a tail clip These tests "show that l-bromo-2,2,2-trifluoroethyl difluoromethyl ether is a potent anesthesia agent which is rapidly taken up and excreted by warm-blooded mammals. This anesthetic produced muscle flaccidity during maintenance, and, in high concentrations caused marked respiratory depression which did not persist into the recovery period. The anesthetized anima ls recovered rapidly and appeared fully alert. In comparison with the l-chloro-2,2,Z-trifluoroethyl difluoromethyl ether anesthetic agent of my U.S. Pat. No. 3,535,425 the anesthesia of the present invention gives comparable induction times in lesser concentrations. Thus with mice, 2.5 percent of the agent of my prior patent gave an induction time of 30 seconds which was accomplished with only'l .5 percent of the anesthesia of this invention.

The anesthetic agent of the invention may be administered by any of the well known techniques used for the administration of general inhalation agents, such as the open drop, semiclosed, and closed systems. The agent may also be administered as an injectable anesthetic as taught by John C. Krantz, Jr. in U.S. Pat. No. 3,2l6,897 issued Nov. 9, 1965 and assigned to the assignee of the instant application.

The compound 1-bromo-2,2,2-trifluoroethyl difluoromethyl ether exhibits excellent anesthetic properties. The compound is non-flammable and soda lime stable. It lends itself to effective use as an inhalent anesthetic in respirable mixtures containing life-supporting concentrations of oxygen as well as mixtures containing oxygen and other inhalation anesthetics such as nitrous oxide. The effective amount of CF CHBr-O-Cl-IF 2 to be employed depends on the level of anesthesia to which the mammal is to be brought, the rate at which anesthe sia is to be induced, and the length of time over which anesthesia is to be maintained. Volume percentages of CF CHB'r-O-CHF in oxygen from a fraction of a percent, e.g. 0.1 to 0.25 percent, up to several percent, e.g. about 10 percent, can be employed. The amount of anesthesia to be used can be easily regulated, starting with a small amount of the ether and gradually increasing the amount until the desired plane of anesthesia is reached. By then monitoring the physical reactions of the mammal, as is the usual procedure, the duration and plane of anesthesia can be readily controlled.

While there has been described what are at present considered to be the preferred embodiments of the invention, it will be understood that various modificaanesthetic amount of 1-bromo-2,2,Z-trifluoroethyl difluoromethyl ether along with sufficient oxygen to support life.

3. A method of anesthetizing an inhalation anesthetic-susceptible mammal which comprises administering to said mammal by inhalation an amount of l-bromo-2,2,2-trifluoroethyl difluoromethyl ether sufficient to induce anesthesia.

UNITED STATES PATENT OFFICE CERTIFICATE OF CORRECTION Patent No. 3,76%,705' Dated October 9 1973 Inventofls) ROSS C TERRELL It is certified that error appears in the above-idehtified patent and that said Letters Patent are hereby corrected as shown below:

Col. 1, line 10, "CH CHBr-O-CHF should read CF CHIBr-OCHF line 29, "CH3CH2OCHF2" should'read cFgcn ocnF line 38, "CH3CH2-O-CHF2" should read I CF3CH2-O-CHF2 line 45, "CH CH O-CI-IF should read a CF3CH2O-CHF2 C01; 2, In the Table, the last two columns run into one another.

Signed and sealed this lL th day of May 19714..

(SEAL) Attest:

EmARD M.FLETCHER,JR. c. MARSHALL DANN' Attesting Officer I Connnissioner of Patents 

2. A method of anesthetizing an inhalation anesthetic-susceptible mammal which comprises administering to said mammal by inhalation an effective, anesthetic amount of 1-bromo-2,2,2-trifluoroethyl difluoromethyl ether along with sufficient oxygen to support life.
 3. A method of anesthetizing an inhalation anesthetic-susceptible mammal which comprises administering to said mammal by inhalation an amount of 1-bromo-2,2,2-trifluoroethyl difluoromethyl ether sufficient to induce anesthesia. 